We are investigating various aspects of the molecular and cellular basis for somatosensation. These studies have included further investigation of itch signaling, examination of the primary neurons involved in detection of thermal stimulation, and those important in spinal cord processing of thermal stimuli. Our studies have used a variety of techniques aimed at determining the cellular and the molecular mechanisms underlying these processes. We are using optogenetics and chemogenetics to precisely define neuronal involvement and the location of these units in sensory pathways. Using mutant mice lacking genes in specific tissues has allowed us to pinpoint and validate the contribution of signaling components. Pharmacological characterization and selective cellular ablation has further allowed us to explore the processes taking place in these pathways. Lastly, we have been using cell-sorting of genetically labeled neurons coupled with NextGen sequencing to search for novel molecules required for the detection, signaling, and transmission of somatosensory stimuli. Our studies reveal that somatosensory discrimination is achieved at the periphery by sensory neurons which detect specific stimuli and transmit signals to dedicated signaling pathways.